Cell cycle-dependent phosphorylation by a CDK inhibits Rb target binding and allows cell cycle progression. Rb inactivation and subsequent cell cycle progression likely requires an initial phosphorylation by cyclin D-CDK4/6 followed by cyclin E-CDK2 phosphorylation. Specificity of different CDK/cyclin complexes has been observed in vitro and cyclin D1 is required for Ser780 phosphorylation in vivo.
